Substrate coating from pulsed plasma polymerization of a macrocycle

ABSTRACT

Devices, and their method of production, having coatings deposited by pulsed plasma polymerization of a macrocycle containing a heteroatom, wherein the heteroatom is oxygen, nitrogen, sulfur, or a mixture thereof The coatings on contact lens are preferably deposited by gas phase polymerization of a cyclic ether, such as crown ether, which coatings are non-fouling and wettable, and the gas phase polymerization utilizes a pulsed discharge.

[0001] This is a continuation-in-part application of prior U.S. patentapplication Ser. No. 09/115,860, filed Jul. 15, 1998, which is acontinuation-in-part application of prior U.S. patent application Ser.No. 08/632,935, filed Apr. 16, 1996, and which claims the benefit ofU.S. Provisional Application Serial No. 60/055,260, filed Aug. 8, 1997,entitled “NON-FOULING WETTABLE COATED DEVICES,” each of which iscommonly assigned with the present invention and the entire content ofeach of which is hereby incorporated by reference.

[0002] The US Government has certain rights in the present inventionpursuant to the National Institutes of Health under Grant R01 AR43186and by the State of Texas through the Texas Higher EducationCoordinating Board ATP Program under Grant 003657-137.

BACKGROUND

[0003] This invention relates to devices having coatings depositedthereon and their method of production. Specifically, this inventionrelates to devices, and their method of production, having coatingsdeposited by pulsed plasma polymerization of a macrocycle containing aheteroatom, wherein the heteroatom is oxygen, nitrogen, sulfur, or amixture thereof More specifically, this invention relates to devices,and their method of production, having coatings deposited by gas phasepolymerization of a cyclic ether, which coatings are non-fouling andwettable, and the gas phase polymerization utilizes a pulsed discharge.

[0004] Non-biologically fouling, wettable thin film surface coatings areof interest for use in improving the biocompatibility of contact lenses.Coatings containing ethylene oxide (—CH₂—CH₂—O)_(n) (“EO”) units arequite effective in providing non-fouling, relatively hydrophilicsurfaces. In particular, it has been recently demonstrated that undercontinuous-wave conditions, volatile, low molecular weight moleculescontaining relatively few EO units can be plasma polymerized ontosurfaces to provide wettable, non-fouling thin film coatings [G. P.Lopez, B. D. Ratner, C. D. Tidwell, C. L. Haycox, R. J. Rapoza, and T.A. Horbett, “Glow discharge plasma deposition of tetraethylene glycoldimethyl ether for fouling-resistant biomaterial surfaces,” J. Biomed.Mater. Res., 26, 415-439 (1992). D. Beyer, W. Knoll, H. Ringsdorf, J.-H.Wang, R. B. Timmons, and P. Sluka, “Reduced protein adsorption onplastics via direct plasma deposition oftriethylene glycol monoallylether,” J. Biomed. Mater. Res., 36, 181-189(1997)]. U.S. patentapplication Ser. No. 09/115,860 disclosed that monomers containing asfew as two EO units per molecule, when plasma polymerized under lowpower input conditions made available by the variable duty cycle pulsedplasma technique, yielded strongly adherent, wettable, and non-foulingcoatings when deposited on the surfaces of contact lenses. The monomersemployed involved only non-cyclic linear or branched olefinic compounds.

[0005] Cyclic ethers, more commonly referred to as crown ethers,represent a separate class of EO molecules containing several oxygenatoms, usually in a regular pattern. Recent reports have shown thatcontinuous-wave plasma polymerization of these compounds can providesurface coatings which exhibit a modest level of biomolecule rejection[E. E. Johnston, B. D. Ratner, and J. D. Bryers, “RF plasma depositedPEO-like surfaces that inhibit Pseudomonas aeruginosa accumulation,”Polym. Mater. Sci. and Engi. (Abstracts), 77, p. 577 (1997). E. E.Johnston and B. D. Ratner, “The effects of linear and cyclic precursorson the molecular structure of ether-rich plasma-deposited films,” Mater.Res. Soc. (Abstracts), p. 464, December 1998 (Boston, Mass.); E. E.Johnston, B. D. Ratner and J. D. Bryers, NATO ASI Series E, AppliedScience, Vol 346, pp.465476, (1997)]. Inthis work, reduced fouling wasdemonstrated with measurements of Pseudomonas Aeruginosa adherence toplasma modified surfaces versus uncoated glass surfaces. For example, anapproximate 40% reduction in Ps. Aeruginosa adherence was observed onplasma polymerized 12-crown-4 (C₈H₁₆O₄) surfaces relative to thatobserved with uncoated glass, as estimated from the graphic dataprovided [E. E. Johnston, B. D. Ratner, and J. D. Bryers, “RF plasmadeposited PEO-like surfaces that inhibit Pseudomonas aeruginosaaccumulation,” Polym. Mater. Sci. and Engi. (Abstracts), 77, p. 577(1997)]. Slightly higher reduction in adsorbed bacteria (i.e., a fewpercent higher) was reported on coatings obtained from the plasmapolymerization of 15-crown-5 (C₁₀H₂₀O₅). The level of protein adsorptionwas observed to be independent of the power input provided during theplasma polymerization of this monomer. Additionally, the crown ethercompounds were shown to be considerably less efficacious than coatingsobtained from linear, saturated EO containing molecules (commonlyreferred to as glymes) of general formula CH₃(OCH₂CH₂)_(n)OCH₃. Forexample, tetraglyme (C₁₀H₂₂O₅) was shown to reduce Ps. Aeruginosasurface adsorption by a factor of at least five times more than thatobserved with the comparable molecule weight 15-crown-5 monomer.Furthermore the tetraglyme coatings deposited at higher plasma power (20W) were shown to adsorb less bacteria than that obtained on coatingsdeposited at 5 W [E. E. Johnston, B. D. Ratner, and J. D. Bryers, “RFplasma deposited PEO-like surfaces that inhibit Pseudomonas aeruginosaaccumulation,” Polym. Mater. Sci. and Engi. (Abstracts), 77, p. 577(1997)]. Thus, in summary, the reported work showed that: (1) Theaccumulation of bacteria onto the linear glyme films was much lower thanthat on the crown ether films, indicating that cyclic ethers producesignificantly poorer non-fouling coatings than the linear glymemolecules when deposited as plasma polymer films on substrates; and (2)the efficacy of the plasma films in functioning as non-fouling coatingsis either independent of the power employed during the plasma deposition(as shown for cyclic ethers) or they become less efficacious withdecreasing power (as shown for the linear glyme).

[0006] Additional notable aspects of the prior studies is that samplesto be coated were located upstream of the plasma discharge zone,apparently in order to improve retention of the EO content in the plasmafilms [E. E. Johnston, B. D. Ratner, and J. D. Bryers, “RF plasmadeposited PEO-like surfaces that inhibit Pseudomonas aeruginosaaccumulation,” Polym. Mater. Sci. and Engi. (Abstracts), 77, p. 577(1997); E. E. Johnston, B. D. Ratner and J. D. Bryers, NATO ASI SeriesE, Applied Science, Vol 346, pp. 465-476, (1997)]. Also, a relativelyhigh (80 W) initial deposition was employed to provide a sub-surfacewhich was apparently required to enhance adhesion of the subsequentoutermost layers deposited at lower power inputs [E. E Johnston, B. D.Ratner, and J. D. Bryers, “RF plasma depositedPEO-like surfaces thatinhibit Pseudomonas aeruginosa accumulation,” Polym. Mater. Sci. andEngi. (Abstracts), 77, p. 577 (1997); E. E. Johnston, B. D. Ratner andJ. D. Bryers, NATO ASI Series E, Applied Science, Vol 346, pp. 465-476,(1997)].

SUMMARY

[0007] The present invention is directed to a device having a substrateand a coating composition, the coating composition being formed bypolymerization of a gas consisting of at least one macrocycle whichcontains, besides carbons and hydrogens, at least one hetero atom,wherein the gas polymerization utilizes a pulsed discharge and whereinthe hetero atom is oxygen, nitrogen or sulfur. The macrocycle can be acyclic ether, such as an ethylene oxide, a dioxane, a crown ether, or amixture thereof.

[0008] The present invention is also directed to a method for plasmadepositing a coating to a solid substrate by subjecting a macrocycle toa gas phase polymerization utilizing a pulsed discharge.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] FIGS. 1(a-e) show high resolution C(1s) ESCA spectra of12-crown-4 films plasma polymerized at 25W peak power. RF duty cycle(on/off times or on/off ratio in ms) employed during formation of eachfilm are: (a) 0.1/1; (b) 0.1/2; (c) 0.1/4; (d) 0.1/8; and (3) 0.1/12;

[0010]FIG. 2 shows variation of C—O/C—C ratio in the pulsed plasmapolymerized 12-crown-4 films as a function of the average power employedduring coating process;

[0011]FIG. 3 shows an FTIR transmission spectra of a series of12-crown-4 plasma polymeric films and 12-crown-4 monomer (bottom). Thespectra reading from top to bottom are arranged in order of increasingpeak powers employed during deposition at RF duty cycle of 0.114 ms;

[0012]FIG. 4(a-c) show high resolution C(1s) XPS spectra of plasmapolymerized 12-crown-4 films. RF duty cycle (on/off times or on/offratio in ms) employed during formation of each film is 0.1/4 ms. Thepeak powers are: (a) 100W; (b) 50W; (c) 25W, respectively;

[0013]FIG. 5 shows water contact angle of pulsed plasma polymerized12-crown-4 films as a function of RF peak power;

[0014]FIG. 6 shows water contact angle of pulsed plasma polymerized12-crown-4 films as a function of the plasma off time under coatingcondition of plasma on time of 0.1 ms and RF peak power of 25W;

[0015] FIGS. 7(a-c) show high resolution C(1s) ESCA spectra of12-crown-4 films plasma polymerized at 25W peak power. RF duty cycle(on/off times or on/off ratio in ms) employed during formation of eachfilm are: (a) 10/400 ms; (b) 1/40 ms; and (c) 0.1/4 ms;

[0016]FIG. 8 shows the variation in water contact angle of pulsed plasmapolymerized 12-crown-4 with changes in the plasma on to off pulsed widthemployed during deposition;

[0017]FIG. 9 shows a comparison of C(1s) XPS high resolution spectra of12-crown-4 plasma deposited films obtained under coating condition 0.1/8ms 25W: (a) fresh sample, (b) after soaking in PBS at 37° C. for 15days; (c) after exposure to PBS flow for 120 hours; and (d) afterexposure to PBS flow for 240 hours;

[0018] FIGS. 10(a-b) show the variation in albumin absorption andretention of pulsed plasma polymerized 12-crown-4 as a function of: (a)RF peak power; and (b) plasma off time; and

[0019] FIGS. 11(a-b) show the variation in fibrinogen absorption andretention of pulsed plasma polymerized 12-crown-4 as a function of: (a)RF peak power; and (b) plasma off time.

DETAILED DESCRIPTION

[0020] Broadly, the present invention pertains to a device having asubstrate and a coating composition, the coating composition beingformed by a gas phase polymerization of a gas consisting of at least onemacrocycle which contains at least one hetero atom, wherein the gaspolymerization utilizes a pulsed discharge and wherein the hetero atomis oxygen, nitrogen or sulfur.

[0021] A macrocycle is a cyclic compound containing, besides carbon andhydrogen atoms, at least one hetero atom, such as, oxygen nitrogen,sulfur, or a mixture thereof A macrocycle can be monocyclic, bicyclic orcycles of higher order. Bicyclics and cycles of higher order includecryptans and spherands. A preferred macrocycle of the present inventionincludes a cyclic ether, such as ethylene oxide, dioxane, and crownether. More preferably, the macrocycle of the present invention includescrown ether. Crown ethers are monocyclic and are relatively large-ringcompounds of carbons and hydrogens containing several oxygen atoms,usually in a regular patterns. Examples or crown ethers include12-crown-4,15-crown-5,18-crown-6,dicyclyhexano-18-crown-6,4′-aminobenzyl-15-crown-5,2-(aminomethyl)-12-crown-4,2-(aminomethyl)-15-crown-5,2-(aminomethyl)-18-crown-6,1-aza-12-crown4,1-aza-15-crown-5,1-aza-18-crown-6,benzo-12-crown-4, benzo-15-crown-5, benzo-18-crown-6,bis[(benzo-15-crown-5)-15-ylmethyl]pimelate, 4′bromobenzo-18crown-6,dibenzo-18-crown-6, dibenzo-24-crown-8,dibenzo-30-crown-10,ar,ar′-di-tert-butyldibenzo-18-crown-6,dicyclohexano-24-crown-8,4′-formylbenzo-15-crown-5,2-(hydroxytmethyl)-12-crown-4,2-(hydroxymethyl)-15-crown-5,2-(hydroxymethyl)-18-crown6,4′nitrobenzo-15-crown-5, andpoly[(dibenzo-18-crown-6)-co-formaldehyde].

[0022] The present invention also pertains to a method for plasmadepositing a coating to a solid substrate by subjecting a macrocycle toa gas phase polymerization utilizing a pulsed discharge. The solidsubstrate of the present invention can be contact lens or biomaterials,such as medical implants.

[0023] In one embodiment, the present invention pertains to the plasmapolymerization of a cyclic ether, such as a crown ether, as a potentialroute for synthesis of wettable, non-fouling coatings, with a particularfocus on applying these films to contact lenses. In contrast with thecontinuous-wave plasma operational mode employed in prior studies ofcrown ethers [E. E. Johnston, B. D. Ratner, and J. D. Bryers, “RF plasmadeposited PEO-like surfaces that inhibit Pseudomonas aeruginosaaccumulation,” Polym. Mater. Sci. and Engi. (Abstracts), 77, p. 577(1997). E. E. Johnston and B. D. Ratner, “The effects of linear andcyclic precursors on the molecular structure of ether-richplasma-deposited films,” Mater. Res. Soc. (Abstracts), p. 464, December1998 (Boston, Mass.); E. E. Johnston, B. D. Ratner and J. D. Bryers,NATO ASI Series E, Applied Science, Vol 346, pp. 465-476, (1997)],pulsed plasma polymerizations were employed here. As an importantexample of the pulsed plasma approach, it was noted that it was possibleto deposit wettable, adherent, and non-fouling coatings from the monomer12-crown-4 under a pulsed plasma duty cycle of 0.1 ms plasma on, 8 msplasma off, and 25 W peak power. From the equation given below, thiscorresponds to an average power input of only 0.31 W. Thus pulsed plasmatechnique of this invention offers the substantial advantage ofdepositing plasma films at average power inputs which are significantlybelow usable values under continuous-wave conditions. By way ofcomparison, it was noted that using the same reactor and identicalmonomer flow rate and pressure as employed during the pulsed run, aminimum of 6 W power input was required to obtain a sustained plasmadischarge and film formation. For reasons documented below, the abilityto deposit high-quality plasma films at ultra low power inputs is ofpivotal importance in obtaining more efficacious non-fouling, highlywettable coatings in films obtained from the crown ethers.

[0024] Detailed studies were carried out using the monomers dioxane(nominally 6-crown-2), 12-crown-4, and 15-crown-5. Films obtained werecharacterized by X-ray photoelectron spectroscopy (XPS) and Fouriertransform infrared spectroscopy (FT-IR). Surface wettabilities weremeasured using a Rame-Hart goniometer and the static sessile drop watercontact angle method. The UV-visible transmission spectra of the plasmafilms were also recorded via deposition of the samples on quartz plates.The adherence and stability of the plasma films were measured using avariety of methods, including prolonged soaking, extended exposure toflow, and abrasive cleaning using common commercial cleansers. Thenon-fouling properties of the coatings were examined via measurements ofprotein surface adsorption using radio-labeled proteins.

[0025] Studies were carried out in which the above-noted film propertieswere examined as a function of the pulsed plasma duty cycles employedduring film formation. With all monomers examined, an enhanced retentionof the EO content of the starting monomers was observed in the plasmafilms as the plasma power employed during film formation was decreased.The relationship between film EO content and average power input wasfound to be highly non-linear in nature, with particularly dramatic (andadvantageous) compositional changes observed at the ultra low powerinputs available under pulsed, but not continuous-wave, depositionconditions. The structure composition and properties of the plasma filmswere found to vary in relatively similar fashion for all three monomersstudied.

[0026] The plasma reactor and general operating conditions were similarto those previously described [V. Panchalingam, X. Chen, C. R. Savage,and R. B. Timmons, “Molecular tailoring of surfaces via pulsed RF plasmadepositions,” J. Appl. Polym. Sci.: Appl. Polym. Symp., 54, 123-141(1994)]. and successfully employed in prior generation of wettable,non-fouling coatings using olefinic EO containing monomers [D. Beyer, W.Knoll, H. Ringsdorf, J.-H. Wang, R. B. Timmons, and P. Sluka, “Reducedprotein adsorption on plastics via direct plasma depositionoftriethylene glycol monoallyl ether,” J. Biomed. Mater. Res., 36,181-189 (1997)].

[0027] In this method, coatings are deposited on solid substrates viaplasma polymerization of selected monomers under controlled conditions.The plasma is driven by RF radiation using coaxial external RFelectrodes located around the exterior of a cylindrical reactor.Substrates to be coated are preferably located in the reactor betweenthe RF electrodes; however, substrates can be located either before orafter the electrodes. The reactor is evacuated to background pressureusing a rotary vacuum pump. A fine metering valve is opened to permitvapor of the monomer (or monomer mixtures) to enter the reactor. Thepressure and flow rate of the monomer through the reactor is controlledby adjustments of the metering valve and a butterfly control valve(connected to a pressure controller) located downstream of the reactor.In general, the monomer reactor pressures employed range fromapproximately 50 to 200 mili-torr, although values outside this rangecan also be utilized. It is preferred that the compounds havesufficiently high vapor pressures so that the compounds do not have tobe heated above room temperature (from about 20 to about 25° C.) tovaporize the compounds. Although the electrodes are located exterior tothe reactor, the process of the invention works equally well forelectrodes located inside the reactor (i.e. a capacitively coupledsystem).

[0028] The chemical composition of a film obtained during plasmadeposition is a strong function of the plasma variables employed,particularly the RF power used to initiate the polymerization processes.It is preferred to operate the plasma process under pulsed conditions,compared to continuous wave (“CW”) operation, because it is possible toemploy reasonably large peak powers during the plasma on initiation stepwhile maintaining a low average power over the course of the coatingprocess. Pulsing means that the power to produce the plasma is turned onand off. The average power under pulsing is defined as:${{Average}\quad {Power}} = {\frac{{plasma}\text{-}{on}\quad {time}}{{{plasma}\text{-}{on}\quad {time}} + {{plasma}\text{-}{off}\quad {time}}} \times {Peak}\quad {Power}}$

[0029] For example, a plasma deposition carried out at a RF duty cycleof 10 msec on and 200 msec off and a peak power of 25 watts correspondsto an average power of 1.2 watts. The Peak Power is preferably betweenabout 10 and about 300 watts.

[0030] The formal definition of duty cycle is defined as the ratio ofthe plasma on time (i.e. discharge time) to a sum of the plasma-on timeand the plasma-off time (i.e. non-discharge time), as represented below:${{Duty}\quad {cycle}} = \frac{{plasma}\text{-}{on}\quad {time}}{{{plasma}\text{-}{on}\quad {time}} + {{plasma}\text{-}{off}\quad {time}}}$

[0031] However, for convenience, the plasma on to plasma off times arefrequently cited herein as a simple ratio of on to off time, both timesemploying the same scale (i.e. milliseconds or microseconds).

[0032] The workable range of duty cycle is less than about ⅕, thepreferred range is between about {fraction (1/10)} and about {fraction(1/1000)}, and the more preferred range is between about {fraction(1/10)} and about {fraction (1/100)}. The plasma-on time should belarger than about 1 μsec, preferably in the range of between about 10μsec and about 100 msec, and more preferably in the range of betweenabout 100 μusec and about 10 msec. The plasma off time, i.e. thenon-discharge time, should be larger than about 4 μsec, preferably inthe range of between about 100 μsec and 2000 msec, and more preferablyin the range of between about 200 μsec and about 100 msec. The totaldeposition time varies depending on the monomer and the conditions used.Typically, the deposition time can vary from about 0.5 min to about 3hours.

[0033] Pulsed plasma deposition permits use of relatively high peakpowers while simultaneously maintaining relatively low average powerswhich provides for the retention of monomer functional groups. Coatingcompositions deposited under low average power pulsed conditions tend tobe more adhesive to a given substrate when compared to films depositedat the same average power but under CW operation. For a given averagepower, the momentary high peak power available under pulsed conditionsapparently assists in obtaining a stronger grafting of the film to thesubstrate than that obtained under the same average power CW conditions.

[0034] For a given RF peak power, an increased retention of the ethercontent (C—O functionality) of the plasma generated coating is observedas the plasma duty cycle is reduced when working with a given monomer.Alternatively, the chemistry of the coating composition can be variedunder pulsed conditions by working at a single plasma duty cycle butvarying peak powers. There is an increased incorporation of C—Ofunctionality in coating compositions as the peak power is decreased.Surprisingly, the plasma generated film composition can be varied bychanging the plasma on to plasma off pulse widths, at a fixed ratio ofplasma on to plasma off times and at a fixed RF peak power. Although thefilm deposition mode described is one of RF plasma polymerization, thosefamiliar in the art will recognize that other polymerization methods(e.g., microwave plasmas, photo-polymerization, ionizing radiation,electrical discharges, etc.) could also be adapted for this purpose.

[0035] The chemical composition of the films of this invention can bevaried during pulsed plasma deposition, by varying the peak power and/orthe duration of the plasma on and plasma off pulse widths. Thisexcellent film chemistry controllability is achieved without recourse tomodulating the temperature of the substrate during the actual coatingprocess. To produce a coating composition with the preferred ratio ofC—O functionality to C—C functionality, it is preferred that the averagepower of the pulsed plasma deposition is less than about 100 watts, morepreferably less than about 40 watts, most preferably less than about 5watts. The highest ratios of C—O functionality to C—C functionality canbe obtained when the average power is 1 watt and less which provides themost non-fouling and wettable coating compositions. The average pulsedpowers used in this invention are less than the wattage under CWconditions in a similar reactor configuration.

[0036] However, as those skilled in the art will recognize, the actualeffect of peak power input on film composition is dependent on thereactor volume (i.e. power density). In the present invention, thereactor volume is approximately 2 liters. Obviously, if a smallerreactor were employed, the same film composition changes reported hereinwould be achieved at lower peak power inputs. Other reaction variableswhich would influence peak power inputs are reactor pressure andmonomer(s) flow rates. If larger reactor volumes were employed, the samefilm compositional variations could be achieved using higher powerinput.

[0037] The use of lower average power conditions increases the presenceof functional groups, e.g. ether units, in the coatings, but the lessenergetic deposition conditions at lower average power may result inpoorer adhesion of the polymer film to the underlying substrate. Thus,the plasma coating process involves somewhat of a compromise betweenretention of monomer integrity in the plasma generated film and thestrength of the adhesion between the coating and the solid substrate. Inthe case of biomedical devices and contact lenses, the adhesion andoverall stability of the coating composition to the lens substrate is anextremely important consideration.

[0038] One method of applying the coating compositions to the substrateof the present invention is by pulsed plasma coupled with gradientlayering. The duty cycle can be varied, thus creating variable dutycycle. The method can be used to maximize the adhesion of the coatingcomposition and the functionalities present in the coating composition.Films deposited under low average power pulsed conditions tend to bemore adhesive to a given substrate when compared to films deposited atthe same average power but under CW operation. For a given averagepower, the momentary high peak power available under pulsed conditionsassists in obtaining a stronger grafting of the film to the substratethan that obtained under the same average power CW condition. Thisstronger grafting under pulsed conditions is repeated with each plasmaon cycle. The better grafting of the film to the substrate obtainedunder pulsed conditions can be even further enhanced by combining thepulsed deposition with a gradient layering technique. In this process,an initial high power, high plasma duty cycle is employed to graft theplasma generated coating composition tightly to the underlyingsubstrate. The plasma duty cycle is subsequently progressively decreasedin a systematic manner, with each decrease resulting in an increasedretention of the C—O functionality in the coating. In this way, thesuccessive plasma deposited films are tightly bonded to each other. Theprocess is terminated when the exterior film layer has reached thedesired composition. The succession of thin layers, each differingslightly in composition in a progressive fashion from the preceding one,results in a significantly more adhesive composite coating compositionbonded to the substrate than coatings deposited without adjusting thedeposition conditions under a relatively lower plasma duty cycle.

[0039] Gas-phase deposition, particularly plasma depositions, providecoating compositions of substantially uniform thickness. The thicknessesof the coating composition could be between 5 Å and 5 μm, morepreferably between 50 Å and 1 μm, and most preferably between 100 Å and0.1 μm. Using the RF pulsed plasma deposition provides linearity of thethickness of the coating composition with deposition time for a givenplasma duty cycle and fixed monomer pressure and flow rate.

[0040] Samples to be coated (e.g., contact lenses) were located in thecenter of a 12-inch long, 4-inch diameter cylindrical glass reactor(i.e., substrates were placed directly in the plasma excitation zone).Despite the very low average power inputs involved under the pulsedplasma conditions, apparently the periodic relatively high peak powersemployed during plasma on periods provide efficient grafting of thefilms to the substrate. The approach employed here can be contrastedwith that involved with continuous-wave plasma polymerizations of crownethers in which substrates were located upstream of the plasmaelectrodes (i.e., the active plasma zone) [E. E. Johnston, B. D. Ratner,and J. D. Bryers, “RF plasma deposited PEO-like surfaces that inhibitPseudomonas aeruginosa accumulation,” Polym. Mater. Sci. and Engi.(Abstracts), 77, p. 577 (1997); E. E. Johnston, B. D. Ratner and J. D.Bryers, NATO ASI Series E, Applied Science, Vol 346, pp. 465-476,(1997)]. Furthermore, the present pulsed plasma approach obviates theneed for a two-step process in which an initial high-power plasmadischarge is employed to provide initial grafting of the film to thesubstrate [E. E. Johnston, B. D. Ratner, and J. D. Bryers, “RF plasmadeposited PEO-like surfaces that inhibit Pseudomonas aeruginosaaccumulation,” Polym. Mater. Sci. and Engi. (Abstracts), 77, p.577(1997)]. The pulsed plasma polymerization approach employed in thisinvention provides the necessary film adhesion to the substratesachievable via a simple one-step pulsed process.

[0041] A key aspect of the pulsed plasma polymerization approach is thefact that by permitting film formation to occur at ultra low averagepower inputs, it is possible to retain monomer functional groups in theplasma films to a much higher degree than that obtained under higherpower continuous-wave conditions. This is of particular importance inthe present case in that it is important to optimize the EO content ofthe films to provide maximum wettability and non-fouling properties tothe plasma modified surfaces consistent with good adhesion of thesefilms. The pivotal role of the average power input during plasmapolymerization in dictating film compositions is illustrated clearly inFIGS. 1 and 2. FIG. 1 shows the high resolution C(1s) XPS spectra offilms obtained from pulsed plasma polymerization of 12-crown-4 monomerat a series of plasma duty cycles. In this series, plasma on times weremaintained at 0.1 ms and plasma off times varied from 1 ms to 12 ms, asshown. As shown in FIG. 1, the detailed curve-fitting analysis of theC(1s) XPS spectra reveal clearly a dramatic increase in the etherlinkage content of the films (i.e., C—O peaks), relative to thoseobserved for the C—C and C═O peaks, as the plasma off time was increasedthrough the sequence 1, 2, and 4 ms. Further increases in plasma offtimes to 8 and 12 ms resulted in relatively little further changes infilm compositions. Overall, the ether linkage retention in the films wasobserved to increase in a highly non-linear fashion with average powerinput as shown in FIG. 2. In this figure, the ratios of the integratedareas of C—O/C—C peaks obtained from the C(1s) XPS spectra are shown asa function of the average power input during film formation. The datarepresent runs carried out at a range of peak powers and plasma dutycycles. Of particular importance is the dramatic increase in the C—Ofilm content (i.e., ether linkages) which become apparent at averagepower inputs of less than 2 W in a plasma reactor of approximately 2 Lvolume. The significance of this fact is that we were unable to maintainfilm deposition in this same plasma reactor with 12-crown-4 monomer atcontinuous-wave power inputs of less than 6 W, under identical flow andpressure conditions employed in the pulsed runs. Clearly, the pulsedplasma technique, by permitting extension of the plasma polymerizationprocess to ultra average low power inputs, permits maximization of theEO content of the plasma deposited films. As documented in the exampleswhich follow, the enhanced EO retention is important in terms of theresultant physical properties of these films, particularly thoseproperties relating to wettability and biological non-fouling.Surprisingly, and in contrast with the CW results, it was observed thatwhen the cyclic ethers were deposited under low duty cycle pulsedplasms, the non-fouling coatings were of equal efficacy as those of thelinear monomers.

[0042] The following examples are provided to further illustrate thisinvention and the manner in which it may be carried out. It will beunderstood, however, that the specific details given in the exampleshave been chosen for purposes of illustration only and not be construedas limiting the invention.

Example 1

[0043] 12-Crown-4 monomer was plasma polymerized at a pulsed plasma dutycycle of 0.1 ms on and 4 ms off at peak power inputs of 25, 50, and 100W. Substantial variations in film compositions were observed over thisrange of power inputs, as shown in FT-IR and C(1s) XPS spectra of thesepolymers (FIGS. 3 and 4, respectively). The FT-IR spectra showsignificant reductions in formation of-OH (3500 cm⁻¹) and C═O groups(˜1700 cm⁻¹) with decreasing average power inputs during plasmaoperation. Neither of these groups is present in the starting monomerand their (undesired) formation occurs during plasma on periods. Thus,reducing peak power during plasma film formation sharply reduces thepresence of these groups. Also, the FT-IR spectra reveal optimization ofthe C—O band at 1120 cm⁻¹ at low power input relative to otherabsorption bands (e.g., C—H, C═O, and —OH). XPS analyses of these films(FIG. 4) confirm the film composition changes noted in the FT-IR spectrain that a marked increase in C—O/C—C peak areas is observed withdecreasing average power inputs.

Example 2

[0044] Advancing and receding water contact angles were measured for thesame films described in Example 1. A substantial increased wettabilityof the films was observed for the run carried out at lowest power input(i.e., peak power 25 W) relative to the 50 and 100 W runs, as shown inFIG. 5.

Example 3

[0045] Plasma polymers were synthesized from 12-crown-4 monomer at aconstant peak power input of 25 W and pulsed plasma duty cycles (on/offtimes, in ms) of 0.1/1, 0.1/2, 0.1/4 and 0.1/8. Advancing and recedingwater contact angles were measured for films obtained in each of theseseparate runs. The results obtained are shown in FIG. 6. Thewettabilities of the plasma generated films were observed to increasewith decreasing pulsed plasma duty cycle employed during film formation,as evidenced by the decreasing water contact angles with decreasing dutycycle employed (FIG. 6).

Example 4

[0046] A series of pulsed plasma polymerized films were deposited from12-crown-4 monomer at a constant duty cycle ratio of 1/40 (relative onto off times) and 25 W peak power input but with varying plasma pulsewidths. The plasma on to plasma off times employed were 0.1/4, 1/40, and10/400 ms. Relatively small film compositional changes and surfacewettabilities were observed, as shown in FIGS. 7 and 8 by C(1s) XPSspectra and water contact angle measurements, respectively. The smallcompositional changes noted in these three runs, all carried out at anaverage power input of 0.61 W, reveal a slightly enhanced film EOcontent with decreasing plasma on and off pulse widths at constantoverall duty cycles.

Example 5

[0047] The stability and adhesion of the pulsed plasma synthesized filmsfrom 12-crown-4 monomer, obtained over a range of average power inputs,were measured with respect to extended soaking in buffer at 37° C. andwith respect to extended exposure to buffered flow solution. The plasmafilms were deposited on a variety of polymeric substrates, including PETdisks and contact lenses. The surface compositions were determined byXPS and water contact angle measurements before and after the soakingand flow exposure experiments. Remarkably little changes were observedin film compositions after soaking and flow exposure, even in the caseof films deposited at average power inputs as low as 0.31 W. Forexample, FIG. 9 shows the C(1s) XPS spectra of a plasma film depositedat a duty cycle of 0.1/8 ms on/off ratio and 25 W peak power as (a)freshly deposited film, (b) after soaking in PBS solution at 37° C. for15 days, (c) after exposure to PBS flow for 120 hours, and (d) afterexposure to PBS flow for 240 hours. Similarly, only relatively smallchanges in water contact angles were observed after those soaking andflow exposure tests. For example, an advancing water contact angle of35° was obtained for films deposited at 0.1/8 ms, 25 W, after 240 hoursof continuous exposure to PBS flow at 25° C. and a buffer flow rate of30 ml/min.

Example 6

[0048] Protein absorptions were measured on a series of pulsed plasmapolymerized films obtained from 12-crown-4 monomer at various plasmaduty cycles. Protein adsorption measurements were carried out using¹²⁵I-radio-labeled albumin and fibrinogen proteins. Both initial proteinadsorption and retention (i.e., protein resistant to removal bysurfactant SDS wash) values were measured on films deposited on PETsubstrates. Uncoated PET substrates were employed as controls. Dramaticdecreases in protein absorptions were observed on the pulsed plasmapolymerized 12-crown-4 films versus that observed on the uncoated PETcontrols. Furthermore, progressively decreased protein adsorption wasobserved on the films as a function of the lowered plasma duty cycle(i.e., average power input) employed during film formation. Thecorrelation between decreased protein adsorption and decreased powerinput during film formation is shown in FIGS. 10 and 11 for albumin andfibrinogen, respectively. The decreases in protein adsorption are verysubstantial on these crown ether films, ranging to reduction factors ashigh as 10 in the case of the lowest duty cycle deposited films (FIG.11). Both the magnitude of the protein adsorption decreases and thestrong dependence of protein adsorption on the average power inputduring plasma polymerization differ significantly for the pulsed plasmapolymerized films of this investigation relative to that reported undercontinuous-wave conditions [E. E. Johnston, B. D. Ratner, and J. D.Bryers, “RF plasma deposited PEO-like surfaces that inhibit Pseudomonasaeruginosa accumulation,” Polym. Mater. Sci. and Engi. (Abstracts); E.E. Johnston, B. D. Ratner and J. D. Bryers, NATO ASI Series E, AppliedScience, Vol 346, pp. 465-476, (1997)].

Example 7

[0049] Films pulsed plasma polymerized from crown ethers were shown toexhibit essentially no absorption of visible light. For example, theUV-visible absorption spectrum of a 200 nm thick film obtained frompulsed plasma polymerization of 12-crown-4 monomer at a duty cycle of0.1/4 ms and 25 W peak power showed no noticeable film absorption overthe wavelength range of 360 to 900 nm. Transparency of these films inthe visible region of the electromagnetic spectrum is an importantproperty of the films, particularly in applications such as coatings forcontact lenses.

Example 8

[0050] Plasma films deposited from the monomer dioxane were shown tocontain EO units, with the density of EO units increasing as the plasmaduty cycles employed during deposition were reduced. However, theC—O/C—C ratios obtained from C(1s) XPS analyses of these films remainedsubstantially less than those obtained from polymerization of 12-crown4monomer under similar power, duty cycle, and flow conditions.

Example 9

[0051] Plasma films obtained from 15-crown-5 monomer were shown tocontain EO film densities at least as high as those obtained from12-crown-4 monomer. However, the lower vapor pressure of this monomerresulted in very low film deposition rates. The deposition rates wereincreased by heating the monomer reservoir and all-gas inlet transferlines.

[0052] The experiments above using pulsed plasma polymerizations of thecyclic ethers reveal the following:

[0053] (1). Highly effective non-fouling coatings can be obtained bypulsed plasma polymerization of the cyclic ether compounds when they aredeposited at low plasma duty cycles. The efficacy of these films inpreventing biomolecule adsorption is certainly equal to that observedwith linear molecules, such as diethylene glycol divinyl ether (“EO2V”),triethylene glycol monoallyl ether (“EO3A”) and the glymes; and

[0054] (2). the non-fouling character of the pulsed plasma filmsimproves sharply as the average power employed during deposition isdecreased in cyclic ether films obtained via pulsed plasmapolymerization.

[0055] An important aspect of pulsed plasma work is the marked increasein the C—O/C—C ratio of the plasma films as the average power employedduring deposition is decreased. Remarkably, it was shown that filmsdeposited at low average power (and thus containing high ether-linkagefunctional group density) exhibit exceptional stability towards soakingor even prolonged exposure to solution flow at an elevated temperature.

[0056] Although not intending to be bound by theory, it is hypothesizedthat this film stability reflects the strong film grafting to thesubstrate which is provided by the brief plasma on periods. In this way,film deposited during the plasma off period is anchored to the substrateduring each successive plasma on period. Undoubtedly, the fact that thesubstrates are located in the active plasma zone between the RFelectrodes aids in improving film stability. Thus, despite the use oflow average power inputs, the pulsed plasma technique providesdeposition of coatings having high ether content, strong adhesion, andexcellent non-fouling properties.

[0057] In contrast with the experiments described above, the workreported [E. E. Johnston, B. D. Ratner, and J. D. Bryers, “RF plasmadeposited PEO-like surfaces that inhibit Pseudomonas aeruginosaaccumulation,” Polym. Mater. Sci. and Engi. (Abstracts), 77, p. 577(1997). E. E. Johnston and B. D. Ratner, “The effects of linear andcyclic precursors on the molecular structure of ether-richplasma-deposited films,” Mater. Res. Soc. (Abstracts), p. 464, December1998 (Boston, Mass.); E. E. Johnston, B. D. Ratner and J. D. Bryers,NATO ASI Series E, Applied Science, Vol 346, pp. 465-476, (1997)]located their substrates upstream of the plasma discharge zone.Undoubtedly, this was done to enhance the ether content of the films.However, preliminary experiments have indicated that films depositedunder low power CW conditions outside the active plasma region exhibitrelatively poor stability.

What is claimed is:
 1. A device comprising a substrate and a coatingcomposition, said coating composition being formed by a gas phasepolymerization of a gas comprising at least one macrocycle containing atleast one hetero atom, said gas polymerization utilizing a pulseddischarge, wherein said hetero atom is oxygen, nitrogen or sulfur. 2.The device of claim 1, wherein said macrocycle is a cyclic ether.
 3. Thedevice of claim 1, wherein said macrocycle is12-crown-4,15-crown-5,18-crown-6, or a mixture thereof.
 4. The device ofclaim 1, wherein said gas phase polymerization utilizing a pulseddischarge having a duty cycle of less than about ⅕, in which thepulse-on time is less than about 100 msec and the pulse-off time is lessthan about 2000 msec.
 5. The device of claim 1, wherein said gas phasepolymerization utilizing a pulsed discharge having a duty cycle of fromabout {fraction (1/10)} to about {fraction (1/1000)}, and the pulse-ontime is from about 1 μsec to about 100 msec, and the pulse-off time isfrom about 10 μsec to about 2000 msec.
 6. The device of claim 1, whereinsaid substrate is a contact lens or a biomaterial.
 7. The device ofclaim 1, wherein said gas phase polymerization is high voltagedischarge, radio frequency, microwave; ionizing radiation induced pulsedplasma polymerization; pulsed photo induced polymerization; or acombination thereof.
 8. The device of claim 1, wherein said coatingcomposition is gradient layered by systematically decreasing said dutycycle of said gas phase polymerization.
 9. The device of claim 1,wherein said substrate is located in the active plasma zone during saidgas phase polymerization.
 10. The device of claim 1, wherein said pulseddischarge uses an average power inputs of less than about 3 W per literof plasma reactor.
 11. A device comprising a substrate and a coatingcomposition, said coating composition being formed by a gas phasepolymerization of a gas comprising at least a cyclic ether, said gasphase polymerization utilizing a pulsed discharge.
 12. The device ofclaim 1 1, wherein said cyclic ether is12-crown-4,15-crown-5,18-crown-6, or a mixture thereof.
 13. The deviceof claim 11, wherein said gas phase polymerization utilizing a pulseddischarge having a duty cycle of less than about ⅕, in which thepulse-on time is less than about 100 msec and the pulse-off time is lessthan about 2000 msec.
 14. The device of claim 11, wherein said gas phasepolymerization utilizing a pulsed discharge having a duty cycle of fromabout {fraction (1/10)} to abut {fraction (1/1000)}, and the pulse-ontime is from about 1 μsec to about 100 msec, and the pulse-off time isfrom about 10 μsec to about 2000 msec.
 15. The device of claim 11,wherein said substrate is a contact lens or a biomaterial.
 16. Thedevice of claim 11, wherein said gas phase polymerization is highvoltage discharge, radio frequency, microwave; ionizing radiationinduced pulsed plasma polymerization; pulsed photo inducedpolymerization; or a combination thereof.
 17. The device of claim 11,wherein said coating composition is gradient layered by systematicallydecreasing said duty cycle of said gas phase polymerization.
 18. Thedevice of claim 11, wherein said substrate is located in the activeplasma zone during said gas phase polymerization.
 19. The device ofclaim 11, wherein said pulsed discharge uses an average power inputs ofless than about 3 W per liter of plasma reactor.
 20. A method for plasmadepositing a coating to a solid substrate, said method comprising:subjecting a macrocycle to a gas phase polymerization utilizing a pulseddischarge, said macrocycle containing at least one hetero atom, whereinsaid hetero atom is oxygen, nitrogen or sulfur.
 21. The method of claim20, wherein said macrocycle is a cyclic ether.
 22. The method of claim20, wherein said macrocycle is 12-crown-4,15-crown-5,18-crown-6, or amixture thereof.
 23. The method of claim 20, wherein said pulseddischarge has a duty cycle of less than about ⅕, in which the pulse-ontime is less than about 100 msec and the pulse-off time is less thanabout 2000 msec.
 24. The method of claim 20, wherein said pulseddischarge has a duty cycle of from about {fraction (1/10)} to about{fraction (1/1000)}, and the pulse-on time is from about 1 μsec to about100 msec, and the pulse-off time is from about 10 μsec to about 2000msec.
 25. The method of claim 20, wherein said substrate is a contactlens or a biomaterial.
 26. The method of claim 20, wherein said gasphase polymerization is high voltage discharge, radio frequency,microwave; ionizing radiation induced plasma polymerization; photoinduced polymerization; or a combination thereof.
 27. The method ofclaim 20, wherein said pulsed discharge comprises a series of variableduty cycle.
 29. The method of claim 20, wherein said substrate islocated in the active plasma zone during said gas phase polymerization.30. The method of claim 20, wherein said pulsed discharge utilizes anaverage power inputs of less than about 3 W per liter of plasma reactor.